THE  PREPARATION  OF  TRIMETHYLOX AMINE 
AND  ISOMERIC  ALKOXYL  DERIVATIVES 


BY 


JAMES  HERBERT  HIBBEN 

B.  S.  University  of  Illinois,  1920 


THESIS 


Submitted  in  Partial  Fulfillment  of  the  Requirements  for  the 


Degree  of 


MASTER  OF  SCIENCE 


IN  CHEMISTRY 


IN 

THE  GRADUATE  SCHOOL 

OF  THE 

UNIVERSITY  OF  ILLINOIS 


1922 


* 


UNIVERSITY  OF  ILLINOIS 


THE  GRADUATE  SCHOOL 


January  21 j gg_ 


I HEREBY  RECOMMEND  THAT  THE  THESIS  PREPARED  UNDER  MY 


SUPERVISION  BY 


JAi/iES  HERBERT  BIBBER 


ENTITLED  THE  PREPARATION  OP  XRIkEIHYLOXAMINE  ADD 


ISOkERIC  ALKOXYL  DERIVATIVES 


BE  ACCEPTED  AS  FULFILLING  THIS  PART  OF  THE  REQUIREMENTS  FOR 


THE  DEGREE  OF MASTER  OE.  SCIENCE 


KJn  • y 


In  Charge  of  Thesis 

nr,  J.  ^ 


Head  of  Department 


Recommendation  concurred  in* 


Committee 


Final  Examination* 


‘‘Required  for  doctor's  degree  but  not  for  master's 


v 


Digitized  by  the  Internet  Archive 
in  2016 


https://archive.org/details/preparationoftriOOhibb 


TABLE  OF  CONTENTS 


1.  Introduction.  . . ......  1 

11.  Historical 10 

111.  Experimental 12 

IV.  Conclusion 28 

V.  Bibliography 29 

VI.  Acknowledgments 30 


1. 


1.  INTRODUCTION. 


The  ultimate  purpose  in  the  study  of  the  amine  oxide 
derivatives-  more  specif icially  the  isomers  trimethylmethoxy- 
ammoniumhydroxide , (CH3)3NtOCH3)OH,  and  trimethylhydroxy  - 
ammonium  methylate,  (CH3 ) 3N(0H)0CH3  , - is  an  investigation^ 
the  phenomena  involved  with  reference  to  the  oxygen  of  the 
methoxy  groups  on  the  electrolysis  of  these  compounds.  If  it 
can  oe  demonstrated  that  the  methoxy  group  will  function  in 
one  case  as  a negative  ion,  and  in  another  as  a positive  ion 
this  will  contribute  some  evidence  toward  the  explanation  of 
the  isomerism.  Tho  the  experimental  data  thus  far  obtained 
deal  only  with  the  preparation  of  these  isomers,  a resume"  of 
tne  structural  representations  advanced  is  necessary  for  the 
consideration  of  any  possible  formulae  of  the  resultant  comp- 
ounds, as  well  as  any  isomeric  interpretation. 

In  1899  Dunstan  and  Goulding1  prepared  trimethylmefch- 
oxyammoniumhydr oxide  by  the  interaction  of  methyliodide  and 
trimethylamineoxide  and  subsequent  conversion  of  the  ammonium 
iodide  salt  thus  formed  to  the  sulphate  which  was  treated 
with  barium  hydroxide.  Heisenhelmer8  in  1913  by  treating 


2. 


trime thylmethoxyammoniumiodide  with  silver  oxide  obtained 
the  same  compound.  However,  by  treating  the  trime  thy  lhy  dr  oxy- 
chloride with  sodium  methylate  he  obtained  not  trime thy lmeth- 
oxyammoniumhy dr oxide  but  tri me thy lhy dr oxy ammonium  methylate. 
The  reactions  and  decomposition  products  are  as  indicated: 

,0CH3 


1.  (CHs)3N~0  + CH3I  — > (CH3)3Nf 


V 


.OGH: 


2.  (CH3)3N7 

T/ 

''OH 


+ AgsO— » (CH3)3N7 


OCH. 


OH 


,och3 

3.  (KH3)3n(  + » (CH3)3N  + CHsO  + Ha0 . 


b.  (CH3)3N=0  + HC1- 


OH 


(CH3)3N. 


OH 


.OH 


OCH. 


5.  (CH3)3N7  + NaOCHa — > (CH^N7 

NC1 
OH 

6.  (CH3)3  n(  + (CH3)3N=0  + CHaOH. 

\)CH. 


Thru  these  and  similar  reactions  Meisenheimer  came 
to  the  conclusion  that,  in  order  to  obtain  two  sueh  fundam- 
entally different  isomers,  one  of  the  valences  of  the  nitrogen 
atom  was  different  from  the  other  four.  He  rejected  various 

possible  explanations  such  as  the  Werner's  ammonium  formula 

3 

or  oxonsznium  formula  discussed  by  Willstater  , Hantsch  and 

4 . 6 

G-ra.f  , Yferner.  In  contrast  to  Werner,  Meisenheimer  assumed 
that  all  five  radicals  were  bound  by  principal  valences  but 


'•  '•  ’ r '■  : ■ 


S : C 


. 


f 


■ / 


. 

3 


that  the  fifth  or  different  valence  was  in  the  outer  zone. 

This  was  represented  by: 

1. 

Fromrn  however,  maintained  that  Meisenheimer ' s ex- 
periments were  not  conclusive  and  capable  of  other  interpre- 
tation. He  said  further  that  the  decomposition  of  the  two 
isomers  into  an  aldenyde,  amine,  and  water:  amine  oxide,  and 

alcohol  respectively  was  not  sufficient  to  give  absolute 
proof  of  the  unique  fifth  valency.  Fromm  represents  the  struct- 
ure of  the  first  compound  as: 

/GH3 

(CH3)3N=(X 

noh. 

7 

Jones  in  discussing  the  electronic  tautomer isn  of 
hydroxylamine  and  its  derivatives  represents  the  structural 
and  electronic  tautomerism  as  follows: 

Structural:  1 > 2,  3 — > 4.  Electronic:  1 — , 4~»  2. 


(1) 

+ 

(Ii  )a-N-+0-H  t > 

(H+)3  n±;o 

(2) 

jr 

jr 

(3) 

(H+)8=N+-0-+H£— * 

( H+ ) a N+-0 

(4) 

CH3  ^ch3 

X N OH. 


CH. 


OCH. 


CH3  ch3 

XN 

CH^  X0H 


OCH- 


- 


. 


4. 


The  OH  group  in  formula  (1)  would  act  as  a positive 

hydroxyl  group  giving  tautomer  (2)  which  would  readily 

dissociate  into  active  oxygen  and  ammonia,  as  is  demonstrated 

by  the  oxidation  of  ferrous  hydroxide  to  ferric  hydroxide  by 

hydroxylamine  and  the  conversion  of  the  latter  into  ammonia# 

Jones  further  supposed  that  if  the  hydroxyl  group  could 

f 'unction  positively  in  this  case  then,  provided  that  one 

hydroxyl  group  was  positive  and  the  other  negative,  in  the 

compound:  ~t~ 

♦ /OH 

{ R )3=N.  _ there  should  be  two 

V0H 

isomers  ( electromers ) and  compounds  of  the  type: 


Rx  -t- 

\ OK 

Rs+_iK  ___  should  exist  in 

,/  N0H 

r3 

sterioisoraeric  modifications.  There  exists  the  possibility 
that  the  optical  isomerism  might  persist  even  to  the 
corresponding  amine  oxides  - (RiRsR3+)  K +-0.  That  the 

latter  deduction  is  correct  has  been  demonstrated  by 

e 

Meisenheimer  who  resolved  sueh  an  amine  oxide  into  enantiomorph- 
ous  modifications. 


Therefore,  Jones  asserted,  the  key  to  the  disputed 
formulae  of  trimethylmethoxyammoniumhydroxide  and  trimethyl- 
hy dr oxy ammonium  methylate  lies  in  the  electronic  conception 


’ 


5. 


by  assuming  that,  in  one  case,  the  fourth  valency  is  linked 
to  a positive  hydroxyl  and  the  fifth  to  the  negative  meth- 
oxyl,  and  in  the  other,  the  linkage  is  to  the  positive 
methoxyl  and  negative  hydroxyl  groups  respectively. 

This  arrangement  with  the  decomposition  products 
is  depicted  thus: 


+,  -+0-+CH3C4) 

( Cri3  ) 3N+-O-+H  k 5 ) “ — : 

► (CHa+)3N+±8-4.H  + H3c"-08 

TT  (4) 

( GH3+ ) 3N+i8-+§Ha  (5) 

—4  (ohJ)3n+±o  + CH3+-0-+H. 

d 

Jones  points  out  again  that  the  isomers  (1),  (2), 
are  alike  structurally  but  different  electronically  and  that 
the  only  difference  in  preparation  lies  in  the  order  by  which 
the  groups  are  introduced. 

10 

Michael  in  1920  stated  that  the  acceptance  of  either 
Meiaenheimer ' s or  Jones’  interpretation  involved  far 
reaching  modifications  in  the  present  conception  of  valence, 
that  isomeric  trialky lhydroxylammonium  salts  and  tri^alkyl- 
oxyammonium  derivatives  are  not  known,  and  there  is,  therefore, 
no  experimental  evidence  in  this  field  to  sup  >ort  any  of  the 
foregoing  hypotheses.  The  formula  ascribed  by  Michael  for 
the  compound  resulting  from  the  reaction  of  methyl  iodide  and 
the  trialkylamine  oxide  is  obtained  thus: 


6. 


?/H  /O 

(CH3)3N=0  + CH3I > (0H3)3  Nr-0  + — > (GH3)3NQ  +Hs0— 4 

\/  GH2 

CHS 

(CH3)3  NHOH  + CHgO  > (GH3)3N  + (JHgO  + HsO. 

In  consideration  of  the  Lewis -Langmuir  theory  of 
valency  the  following  structures  might  be  assigned  to  the 
compounds  trimethylmethoxyammoniumhydroxide  and  trimethyl- 
hy dr oxy ammonium  methylate,  using  the  electronic  conception 
of  the  isomerism. 

CW.  h3c  + j (2)  h3g  + ; 

H3C :N:0 :H  ' 0:CHa  H3G :N:OCHo  1 0 :H 

I I 

h3c  * ! h3V  ! 

Wherein  it  becomes  apparent  that,  in  the  second  case, 
the  oxygen  of  the  methoxyl  group  shares  two  electrons  with 
the  nitrogen  , and  the  oxygen  of  the  hydroxyl  group  shares 
two  electrons  only  with  the  hydrogen,  while  the  converse  is 
true  in  case  (lj , that  is,  the  nitrogen  shares  two  electrons 
with  the  oxygen  og  the  hydroxyl  group,  and  the  oxygen  of 
the  methoxyl  group  shares  electrons  only  with  the  CH3  group. 


7. 


It  may  be  readily  seen,  therfore,  that  the  degree  of  attach- 
ment of  these  groups  to  the  nitrogen  is  different.  In  the 

second  isomer  the  methoxyl  group  is  bound  by  a polar  and 

11 

in  the  first  by  a non-polar  valence.  Hence  isomer  (2) 

would  be  expected  to  ionize  into  negative  (OH)  and  positive 

( CH3 ) 3N(OCH3 ) , and  isomer  (1)  would  furnish  the  ions  negative 

(0CH3)  and  positive  (GH3)3N(0H)  . It  is  evident  that  the 

methoxy  group  functions,  if  this  representation  is  correct, 

in  one  case  negatively  and  in  the  other,  positively,  or  in 

the  last  analysis,  the  oxygen  behaves  normally  on  one  hand 

and  on  the  other  as  if  it  were  neutral  or  more  positive  than 

normal  oxygen,  and  with  consequent  greater  oxidation  capacity 

analagous  to  the  oxygen  of  hydrogen  peroxide , such  an  analogy 

having  been  demonstrated  in  the  case  of  the  amine  oxide  by 

12 

Hantzsch  and  Hillard  . The  decomposition,  therefore  of 
the  second  isomer  into  the  amine,  aldehyde  and  water  compared 
with  the  decomposition  of  the  first  isomer  into  the  amine 
oxide  and  methyl  alcohol  might  be  expected. 

From  this  electronic  configuration  it  may  also  be 
seen  that  the  basisity  of  the  trimethylhydroxylammonium 
methylate  will  be  less  than  that  of  the  trirne  thy  line  thoxyl- 
ammoniumhydroxide . If  comparison  is  made  between  tetra- 
methylammoniumhydroxide  and  trime thy lmethoxy ammonium  methylate 


8. 


the  Lewi 3 -Langmuir  conception  of  valency  phenomena  leads 
to  a possible  explanation  of  the  lesser  basisity  of  trie 
latter  compound,  which  might  ue  raised  as  an  objection  to 
the  electronic  representation. 


and  monochloracetic  acid,  the  influence  of  the  increasingly 
electronegative  groups , ( GH3— »H,  H — * Cl  ) is  to  make  a 
stronger  acid,  or  in  other  words,  to  cause  the  hydrogen  of 
the  hydroxyl  group  to  ionize  as  a hydrogen  ion  to  a greater 
and  greater  degree.  Hence  there  is  a seeming  displacement 
of  the  electrons  holding  the  hydrogen,  toward  the  carbon 
atom.  Similarly,  therefore,  the  influence  of  the  oxygen  of 
the  methoxyl  group,  which  is  more  electronegative  than  the 
GH3  group  of  the  t e tr ame thy laurnoni urn  compound  as: 


would  be  to  cause  some  electronic  displacement  between  the 
carbon  atom  and  one  of  the  hydrogens  of  the  methyl  group  as 
follows:  TT 


and  consequent  tendency  of  the  hydrogen  thus  less  closely 
bound  to  neutralize  the  ionized  hydroxyl  group  making  this 
compound  less  basic  than  the  tetramethylammoniumhydroxide. 


Considering  such  organic  acids  as  acetic,  formic, 


(CH3)3N-CHa 

'oh 


and 


H 

=N--0  :C  £:H 
H 


. 


. 


9. 


The  foregoing  discussion  reviews  in  brief  various 
representations  of  the  amine  oxide  derivatives.  The  motive 
has  been  several  fold:  first,  a better  understanding  is 
obtained  of  the  reaction  phenomena  involved  in  their  prepara- 
tion, and  second,  as  has  been  pointed  out,  the  ultimate 
purpose  in  the  preparation  of  these  compounds  is  to  obtain 
experimentally  some  evidence  that  may  contribute  tov/ard  the 
substantiation  or  refutation  of  the  electronic  conception 
of  the  isomerism.  Hence  the  previous  discussion  outlines  to 
some  extent  the  scope  and  point  of  vie?/  in  such  an  attempt. 


HISTORICAL. 


10, 


2. 


In  an  attempt  to  prepare  B-  alkylhydroxylamine  Lobry 

13 

de  Bruyn  in  1894  treated  hydroxylamine  with  methyl  iodide 
obtaining  the  salt  CH3NH0H*HI  according  to  his  analysis. 

14 

Duns tan  and  Moulding  during  the  same  year  while  repeating 
de  Bruyn* s work  obtained  trimethylhydroxylaninehydroiodide 
as  a result  of  the  same  reaction.  In  addition  the  sulphate, 
hydrochloride  and  free  trimethylhydroxylamine  were  prepared 

1 5 

from  the  original  hydroiodide.  Subsequently  Duns tan  and 

Goulding  found  that  in  addition  to  the  trimethylhydroxylamine- 
hydoiodide,  a mixture  of  the  mono,  di , and  tri  hydroiodide  - 
hydroxylamine  (NHa0H*HI,  (NH80H)3HI,  (NHs0H)3HI  ) was  also 

is 

formed.  This  was  substantiated  by  de  Bruyn  who  obtained 
similar  results  in  1896,  admitting  also  the  error  of  his  first 
analysis. 

_ 17 

In  1399  Dunstan  and  G-oulding  investigated  the  prop- 
erties of  the  trialkyl  salts  and  of  the  free  trimethylhydroxyl- 
amine or,  correctly,  trimethylamine  oxide  as  the  derivative 
obtained  in  this  reaction  is  not  a true  hydroxylamine  der- 
ivative, but  an  isomer  of  it.  They  criticised  the  work  of 

is 

Hantzsch  and  Hillard  who  by  a similar  reaction  obtained  a 
compound  which  they  designated  as  a carbonate  instead  of  the 


11. 


amine  oxide.  In  addition  Duns tan  and  Moulding  made  the  tri- 
methylmethoxyammoniumiodide  salt  and  trime thy lmethoxy ammonium - 
hydroxide  at  this  time. 

The  next  important  advancement  was  the  preparation 

18 

of  the  trialkylamine  oxides  by  the  simple  oxidation  of 
trialkylated  amines  by  these  same  investigators  a few  months 

19 

later.  This  was  repeated  by  Meisenheimer  in  1913  who  syn- 
thesized in  addition  several  trimethylalkyloxyammoniuniiodide 
salts  in  addition  to  the  two  isomers,  trime  thy  line  thoxy  ammonium- 
hydroxide  and  trimethylhydroxyammonium  methylate  and  other 
similar  alkyl  substituted  compounds. 


. 


12. 


3.  EXPERIMENTAL. 


The  procedures  employed  in  the  preparation  of  these 
compounds  which  have  been  chronologically  considered,  may 
be  briefly  summarized  by  the  following  equations: 


1.  HsNOH  +3CH3I  V (GH3)3N^  + S-WI. 


.OH 


OH 


, s OH  (GH3)3N( 

2.  2 (CH3)3N/  + Ag8S04 » VS0*  + 2AgI. 

NI  (ch3)3n/ 

OH 


3.  (CH3)3N(OH)  )3S04  + Ba(OH) a— > 2(0H3 ) 3N=0*2HS0  +BaSO. 

4.  ( CH3  ) 3N=0 • 2HgO  + (GH3)3N=0  + 2HgO. 


5.  (CH3)3N  + H80s+H80 — l>  ( SH3  ) 3N=0*  2H80 

OH 


6.  (CH3)3N=0  + HC1 


( CH3 ) 3N^ 

XJl 


7.  (CH3)3N=0  + ch3i  — s>  (gh3)3n/ 


,OCH. 


Vi 


OCH3  och3 

8.2(CH3)3N'  + Ag80-^2(CH3)3N(  + 2AgI. 

NI  '' 


9*  (GH3)3N^  + NaOCH3  — > ( CH3  ) + NaCl. 


OH 


OH 

OH 


\ 


Cl 


bGH. 


10.  (CH3)3N(0H)0CH3  + — > ch3oh  + (ch3)3n=0 


13. 


11.  (CH3)3N(0CH3)0H  4.  -i-*  (CH3)3N  +Ha0  + GHsO. 

For  the  purpose  of  clarity  in  the  consideration  of 
the  preparation  and  properties  of  these  compounds,  each 
individual  will  be  considered  seperately,  the  procedure 

i? 

being  as  outlined  by  Dunstan  and  Moulding  and  by 

19 

Meisenheimer . 

/0H 

(ch3)3n; 

xi 

OH 

HgNOH  +3CH3I  — > ( GH3 ) 3Ir  + 2HI . 

NI 

Methyl  iodide  was  added  to  a dilute  solution  of 
hydroxyl amine  in  methyl  alcohfol  prepared  from  the  interaction 
of  sodium  methylate  and  hydroxylaminehydrochloride . The 
hydrochloride  salt  was  obtained  from  treating  hydroxylamine 
sulphate  with  barium  chloride.  After  the  addition  of  the 
methyliodide  a white  precipitate  separated,  which  on  reflux- 
ing the  mixture  for  a short  time  went  into  solution.  The 
refluxing,  while  preventing  the  formation  of  (NH80H*HI, 
(NHgOH)gHl,  and  (NH8OH)3HI  ) in  as  large  a quantity  as  would 
otherwise  occur,  also  results  in  the  separation  of  free 
hydriotic  acid  due  to  the  partial  decomposition  of  the  salts 
even  at  thi3  temperature. 


14. 


The  excess  of  methyl  alcohol  was  distilled  under 
18  mins  pressure  and  the  trimethylhydroxyainmoniumiodide 
separated  from  the  remaining  hydroxylaminehydroiodide  salts 
by  means  of  fractional  recrystallization  with  ether.  The 
salt  thus  obtained  was  purified  by  recrystallization  from 
hot  alcohol  and  ether.  The  theoretical  yield  from  15  gms. 
of  hydroxylamine  was  91  gms.  A yield  of  8.8  percent  was 
obtained.  Decomposition  began  at  95*  and  became  total  at  125*uc. 
Noticeable  decomposition  was  a,parant  on  exposure  to  sunlight. 

On  a second  attempt  a yield  of  17.2  percent  was  obtained.  The 
higher  yield  in  the  second  case  being  attributed  to  less 
decomposition  during  a shorter  period  of  refluxing.  A pur- 
ified sample  of  the  salt  almost  totally  decomposed  on  ten  days 
standing. 

.OH 

(0H3)3N( 

\so4 

( CH3 ) 3 v/ 

\)H 


2 (GH3)3N^  + Ag8S04  ->(  ( CHS  ) 3N0H  )3S04  +2Ag£. 

NI 

Trimethylhydroxylammoniurnhydroiodide  was  added  to  a 
solution  of  silver  sulphate  in  water,  the  precipitate  of  silver 
iodide  filtered,  and  the  aqueous  solution  evaporated  under 


I 


15. 


diminished  pressure.  The  residue  was  dissolved  in  absolute 
methyl  alcohol,  separating  any  excess  of  silver  sulphate, 
clarified  with  Eastman's  special  bone  black  and  reprecipit- 
ated on  concentration  of  the  solution,  by  the  addition  of 
ether.  The  resulting  sulphate  crystals  were  white,  very  sol- 
uble in  water,  less  soluble  in  ethyl  alcohol,  and  insoluble 
in  ether.  The  crystals  decomposed  at  155*  uc.  and  react  with 
barium  carbonate  to  yield  carbon  dioxide,  the  free  base,  and 
barium  sulphate.  After  several  purifications  to  get  a constant 
decomposition  point,  the  yield  was  40  percent  of  the  theoret- 
ical. 

Later  this  compound  was  prepared  from  the  hydrochloric 
of  tri methyl amine  oxide  in  a similar  manner  but  with  an 
unsatisfactory  yield.  The  hydrochloride  lends  itself  to  pur- 
ification with  greater  facility  than  the  hydroiodide  and  for 
that  reason  was  selected.  However,  on  evaporation  even  under 
diminished  pressure  of  the  aqueous  solution,  after  filtering 
off  the  silver  chloride  the  sulphate  suffered  no  little  dec- 
omposition. The  excess  silver  sulphate  might  plausibly  act 
as  a catalyst  in  such  a decomposition. 


An  analysis  of  the  compound  resulted  in  the  following: 


1 6 . 


( (CH3)3N0H)8  S04. 

1. 

Calculated  Percent  S04  in  substance  . . . 38.67. 

Weight  substance. . .0.2282  gms.  Weight  BaS04 . . . 0. 2453  gms. 

Percent  S04  founda  44.2. 

2. 

Calculated  Percent  S04  in  substance  38.67. 

Weight  substance  ..0.2925  gms.  Weight  BaS04..  0.3187  gms. 

Percent  S04  found 44.75. 

Calculated  molecular  weight  248.  Molecular  weight  from 

analyds..  216. 

A third  method  of  preparation  of  the  sulphate  is 
by  the  direct  action  of  sulphuric  acid  on  trimethylamine  oxide. 
This,  despite  the  difficulty  in  obtaining  the  pure  amineoxide* 
hydrate,  has  resulted  in  a purer  compound  than  the  foregoing 
methods.  The  sulphate  does  not  lend  itself  easily  to  analysis. 


( CHo ) 3N=0 , 


( (CH3)3  N0H)3S04  + Ba( OH) 2 — > ( CHa ) 3N=0- 2HS0  + BaS04 

( CH3 ) 3N  + H§0  + HgOg  } ( CH3 ) 3H=0 * 2HgO . 


17. 


This  compound  may  he  prepared  in  two  ways.  The  first 
method  adopted  was  hy  the  interaction  of  the  previously  des- 
cribed sulphate  with  barium  hydroxide,  the  excess  barium 
hydroxide  being  precipitated  by  passing  carbon  dioxide  thru 
the  solution.  The  aqueous  solution  was  distilled  under  10  6ms 
pressure.  The  residue  was  then  dissolved  in  absolute  methyl 
alcohol  and  recrystallized  with  ether  or  from  hot  ethylic  al- 
cohol solution.  The  resultant  product  isx the  amine  oxide 
with  two  molecules  of  water  of  crystallisation.  The  best 
yield  obtained  was  31.2  percent.  The  hydrated  form  crystallized 
in  radiating  needles  with  a melting  point  of  96' . The  substance 
is  very  deliquescent,  very  soluble  in  water  and  also  in  methyl 
alcohol,  less  soluble  in  ethyl  alcohol  and  insoluble  in  ether. 
It  will  not  reduce  Fehlings  solution,  reacts  alkaline  to 
litmus  and  methyl  orange,  will  not  liberate  I from  KI  and 
quickly  oxidizes  a solution  of  ferrous  sulphate  to  ferric 
hydroxide.  Dunstan  and  Moulding  found,  in  addition,  that 
this  compound  would  react  with  benzyl  chloride  to  form  benz- 
aldehyde  and  trimethylamine. 

13 

Hantzsch  and  Hilland,  on  the  contrary,  obtained  a 
compound  which  would  reduce  Fehlings  solution,  liberate  I 
from  KI  and  absorb  carbon  dioxide.  They  were  led  to  the 


13. 


conclusion  that  the  methoxyammoniumhydrate  could  exist  only 
in  an  ionized  state.  The  results  obtained  substantiate 
Hantzsch  and  Hi Hand  in  only  one  particular,  that  is,  the 
disposition  of  the  hydroiodide  and  me thoxy iodide  salts 
of  trimethylamine  oxide  to  liberate  iodine. 

A small  quantity  of  the  free  trimethylamine  oxide 
was  obtained  by  subliming  the  hydrated  form  at  .5mm  pressure. 
The  original  hydrate  was  heated  in  a tube  ( Plate  1 ) at 
12^*  until  all  bubbling  had  ceased.  After  the  temperature  then 
was  raised  to  150*  for  ten  minutes,  the  hydrate  was  caied 
and  subsequently  reheated  at  190-200*  for  one  and  one  half 
hours.  Subliminal  ion  began  at  180*  . Only  after  repeated  attempts: 
however,  were  these  results  obtained.  A small  amount  of  impur- 
ity will  cause  the  decomposition  of  the  dehydrated  form  to 
begin  at  17°'-l8Q*  instead  of  205*  (Meisenheimer  used  a 
pressure  of  10-12  mm.  His  product  decomposed  at  2^8* ) The 
pure  trimethylamine  oxide  is  extremely  hygroscopic  and  virt- 
ually impossible  to  obtain  in  any  practical  quantity.  Phos- 
phorous pentoxide  and  calcium  chloride  were  used  as  drying 
agents  in  the  neck  of  the  sublimination  tube. 

Hence  it  may  be  seen  that  the  preparation  of  the 


VLBTE  J — 


19. 


anhydrous  form  by  means  of  the  foregoing  procedure  is  not 
very  satisfactory.  The  method  outlined  for  the  preparation 
of  the  hydrated  form  yields  a net  result  of  approximately 

two  percent.  For  this  reason,  and  because  of  greater  facility 

18 

in  the  preparation,  the  hydrogen  peroxide  method  was 
adopted. 

A three  percent  solution  of  hydrogen  peroxide  was 
added  to  a twenty  nine  percent  solution  of  trimethylamine 
and  the  solution  allowed  to  stand  twenty  four  hours  when, 
if  the  trimethylamine  odor  had  not  yet  disappeared,  more 
hydrogen  peroxide  was  added.  The  large  volume  of  water  was 
evaporated  off  under  l3  cms  pressure  until  a viscious  brown 
nonvolatile  residue  remained.  This  was  redissolved  in  methyl 
alcohol  and  crystallized  with  ether.  Several  recrystallizatiors 
were  necessary  to  obtain  a corstant  melting  point  of  95*. 

The  compound  ansv/ers  the  description  previously  given  for 
trimethylamine oxidehydrate . The  yield  was  thirty  percent. 

It  was  noticed*  that  the  heating  effect  of  the  reaction  drove 
off  the  trimethylamine  so  that  by  connecting  the  mouth  of 
the  vessel  in  which  the  solutions  were  allowed  to  stand  to  a 
curved  mercury  column  thus  allowing  for  expansion  and  prevent- 
ing the  escape  of  the  trimethylamine  . The  maximum  yield  was 
eighty  percent.  ( Meisenheimer  90-95  ) . 


20. 


(CH3)3N 


.OCHs 


i 

(GHs)sN=0  + CH3I  » (OH3)3Nv/ 

V 


,OCH« 


The  above  equation  represents  the  use  of  the 
dehydrated,  base.  In  the  actual  experiments,  however, 
on  account  of  the  difficulty  in  obtaining  and  handling 
the  anhydrous  forin^  the  hydrated  base  was  used  throughout. 
There  was  no  appreciable  derogatory  effect. 

A solution  of  the  tri methyl amine  oxide  in  water 
is  not  used  in  these  reactions  because  of  the  difficulty 
encountered  in  recovering  the  soluble  products  without 
decomposition.  Hence  an  alcoholic  solution  of  trimethylamine 
oxide  is  added  to  methyliodide  and  the  mixture  allowed  to 
stand  in  a sealed  jar  for  forty  eight  hours.  The  methoxy- 
iodide  , which  is  soluble  in  water,  hot  methyl  alcohol  and 
insoluble  in  ether,  was  crystallized  from  an  alcohol  ether 
mixture  in  the  form  of  white  plates.  As  a by-product 
tetramethylammoniumiodide  is  formed  only  to  the  extent  of 
from  five  to  ten  percent  with  proper  precautions.  It  is 
separated  from  the  methoxy  compound  by  dissolving  the  latter 
in  the  minimum  amount  of  methyl  alcohol.  Tne  slightest 
trace  of  impurity  will  cause  the  partial  decomposition  of 


!i 


21. 


the  methoxyiodide  even  at  room  temperature.  The  decomposition 
ranged  from  155'’  to  162**,  ( Meisenheimer  162“)  which  by 
no  means  represents  its  stability  as  a whole.  The  maximum 
yield  obtained  was  53-6  percent.  (Meisenheimer  40  percent  ). 

The  following  analytical  results  were  obtained: 
(0H3)3N(OCHa)l. 

1. 

Calculated  percent  I in  substance 58.58 

Weight  substance..  0.9644  gms.  Wt  Agl  ....1.0365  gms. 
Percent  iodine  found 58.10 

2.  Calculated  percent  I in  substance 58.58. 

Weight  substance  1.2032  gms.  Weight  Agl...  1.2951  gms. 
Percent  iodine  found 58.20 

A sample  of  the  precipitate  insoluble  in  a small 
amount  of  methyl  alcohol,  presumably  tetramethylainmoniumiodide, 
analyses  as  follows: 

(CH3)3N-I. 

1 


Calculated  percent  I in  substance 63.2. 

Weight  substance.  0.4152  gms.  Weight  Agl. 0.4744  gms. 
Percent  iodine  found 61.75 


22. 


The  slightly  too  low  a percent  iodine  from  the  theoretical 
might  be  due  to  the  presence  of  some  of  the  methoxy  iodide 
s al  t • 


(CH3)3< 

Til 


(GH3)3N=0  + HC1 » (GH3)3n( 

XC1 

The  trimethyloxaminehydro chloride  is  prepared  by 
the  direct  action  of  hydrochloric  acid  on  the  amine  oxide. 

It  is  the  most  stable  of  all  the  salts  obtained.  The  aqueous 
solution  was  evaporated  over  a steam  bath  to  dryness,  the 
residue  was  then  crystallized  from  hot  methyl  alcohol  by 
cooling  and  adding  ether,  or  by  repeated  cooling  and  filter- 
ing with  subsequent  evaporation.  The  yield  was  93  percent. 

The  compound  is  soluble  in  water,  hot  methyl  alcohol,  and 
insoluble  in  ether.  It  melts  without  decomposition  at  212* uc. 
(Dunstan  and  Moulding  205p-210‘ ) 


( CH3)3N  (OCH3)  OH. 


,och3 

2 (CH3)3N'  + Ag80 


.0CH3 

Ndh 


►2  ( CH3  ) 3N  ^ + 2AgI 


23. 


This  compound  has  been  prepared  only  in  solution. 

The  trimethylmethoxy iodide  salt  in  dilute  aqueous  solution 
is  added  to  a molecular  proportion  of  silver  oxide,  the 
silver  iodide  formed  filtered  off,  and,  for  identification 
purposes,  the  solution  acidified  with  hydrochloric  acid, 
wherein,  on  subsequent  evaporation,  there  remains  behind! 
the  hygroscopic  crystalline  trimethylmethoxyarnmoniumchloride. 
The  chloride  can  be  determined  by  conversion  to  the  chlor- 

19 

platinate.  Meisenheimer  found  that  the  base  decomposed 
completely  o#  evaporation  of  the  solution  and  he  quantatively 
determined  the  trimethylamine  and  formaldehyde  formed  on 
decomposition. 

As  has  been  pointed  out  in  the  introduction,  this 
compound  and  trimethylammoniumhydroxyl  methylate  are,  if 
possible,  to  be  electrolysed.  For  that  purpose  it  is  extrem- 
ely essential  that  they  be  obtained  in  a pure  state. 

On  account  of  the  instability  of  the  methoxy  iodide, 
and  the  fact  that  the  sulphates  have  uniformly  been  more  stable 
than  the  iodides,  an  attempt  was  made  to  prepare  the  tri- 
methylmethoxy lammonium  sulphate  by  converting  the  iodide  with 
silver  sulphate.  This  was  not  successful  for  after  stirring 
for  several  hours  and  subsequent  evaporation  of  the  water 
solution  under  diminished  pressure,  noticeable  decomposition 


24. 


ensued.  The  trimethylamine  oxide  was  then  treated  with 
dimethyl sulphate  to  obtain  similar  results  according  to 
the  following  reaction: 

OCHs 

(gh3)3  n' 

2 (gh3)3n=o  + (ch3)8so4  — b ;so4 

(ck3)3  n( 

n0CH3 

The  excess  dimethyl sulphate  was  distilled  in  the 
apparatus  (Plate  2 ) which  had  been  previously  ?/eighed. 

Phe  resultant  residue  was  a yellowish,  viscious,  hygroscopic , non 
crystalline  mass.  The  procedure  was  repeated  with  similar 
results.  Quantatively  represented  the  results  were: 

1. 

Calculated  weight  of  substance  from  10  gms  ( CH3 ) 3N=:0 . 2H2C 
12.4000gms. 

Weight  Substance  Found 11.7964  gms  . 

final  weighing  was  made  after  the  complete  removal 
of  any  excess  dimethylsulphate  and  solvent  by  evacuating  to 
a pressure  of  two  millimeters. 

However,  the  residue  being  non  crystalline  would 
not,  therefore,  be  a3  good  a medium  a3  the  trimethylmethoxy- 
ammonium  iodide  for  the  prej^aration  of  trimethylmethoxyammonium- 
hydroxide.  Hence  this  method  was  abandoned. 


' 


. 


\ 


PLRTE 


25. 


By  repeated  recrystallisation  of  the  (CHS) 3N(0CHs)l- 
filtering  the  alcoholic  solution  directly  into  a large  quan- 
tity of  ether  the  quick  precipitation  preventing  the  occlusion 
of  inpurities-  a sufficiently  pure  sample  of  the  methoxy  iodide 
salt  was  obtained.  However,  it  is  only  stable  under  ether 
and  will  decompose  under  warming  or  standing  for  several  days. 
To  an  alcoholic  solution  of  this  sample  at  a temperature  of 
-10  sufficient  potassium  hydroxide  was  added.  The  odor  of 

_ ition  3 Loticeable  even  at  this 

temperature. 


The  solution  was  then  distilled  at  .5mm  pressure 
by  means  of  the  apparatus  in. Plate  3.  The  distillate  was 

, o 

xept  at  -15  and  the  aldehyde  odor  was  only  faintly  apparant. 
Hydrochloric  acid  gas  was  passed  thru  the  alcoholic  solution 
of  the  distillate  which  was  then  evaporated  leaving  a chloride 
residue.  The  samples  used  were  small  and  the  yield  not  suffic- 
ient for  analysis. 

The  experiment  will  be  repeated  in  a like  manner, 
and  also  with  the  use  of  silver  oxide  in  aqueous  solution. 

is  hoped  that,  with  sufficiently  reduced  pressure  and  great 
cooling,  the  trimethylmethoxyammoniumhydroxide  may  be  dis- 
^j-llsd  without  decomposition  and  purified  in  this  manner. 


26. 


(CH3)3N  (OH)  OCHa . 


(CH3)3 
( GH3 ) 3 


OH 

N\ 

>S04 

\0H 


OH 

+ 2 NaOCH3— > 2 (CH3)  3 + NagSO^ 

v0CH3 


The  use  of  the  trimethyloxamine  sulphate  in  place 

19 

of  the  hydrochloride  used  by  Meisenheimer  seems  more 
advisable  because  of  the  greater  insolubility  of  the 
resultant  sodium  sulphate,  consequently  a larger  portion  may 
be  filtered  off  before  attempting  the  distillation  of  the 
trimethylhydroxyammonium  methylate  in  the  manner  just  outlined. 
The  influence  of  impurities  as  catalysers  toward  the  decom- 
position of  the  amine  oxide  derivatives  has  been  pointed  out. 

An  attempt  to  distil  this  compound  was  made  as  ment- 
ioned. The  distillate  showed  no  aldehyde  reaction  with  phenyl 
hydrazine. 


The  work  on  the  trimethylmethoxyammoniumhydroxide 
and  trimethylhydroxyammonium  methylate  will  be  continued. 
Tnere  is  a possibility  that  if  the  distillation  method  of 
purification  should  prove  unsuccessful,  this  might  be  ac- 
complished in  the  same  manner  by  which  Knorr  isolated  the 


27. 


enol  fora  of  acetoaceticester—  co  .'ling  with  carbon  dioxide 
snow. 


It  seems  proper  to  say  that  the  foregoing  results 
were  obtained  only  after  considerable  familiarity  with  the 
compounds  and  the  requisite  manipulation  had  been  acquired. 


28. 


4.  CONCLUSION. 


The  work  of  Duns tan  and  Moulding  and  Jacob  Meisen- 
he&mer  on  the  preparation  of  trimethylamine  oxide  and  alk- 
oxyl  derivatives  has  been  repeated  and  substantiated.  Slight 
variations  in  procedure  have,  in  some  cases,  yielded  improve- 
ment, while  in  others  such  attempts  have  been  without  pos- 
itive results.  Sufficient  quantaties  of  the  derivatives  have 
been  prepared  to  allow  further  experimentation  along  the 
lines  indicated. 

It  is  hoped  that,  with  the  possible  purif ication 
of  the  trialkylmethoxyammoniumhydroxide  and  trialkylhydroxy- 
ammonium  methylate,  that  these  isomers  may  be  subsequently 
electrolysed  and,  as  has  been  pointed  out,  the  results  may 
throw  some  light  upon  the  electronic  conception  of  their 
isomerism. 


29. 


5 BIBLIOGRAPHY. 

1.  Dunstan  and  Moulding.  J.C.S.,  75,  792,  139$. 

2.  Jacob  Meisenheimer.  Ann. ,397,  273,  1913. 

3.  Willstatter . Ber. , 33,  1638,  1900. 

4.  Hantzsch  and  Graf.  Ber. , 33,  2154,  1915. 

5.  Werner.  (Neuere  Anschauug en)  204-210,  19°9. 

6.  Emil  ^romm.  Ann.,  399,  366,  1913. 

7.  Wm.L.  Jones.  J.  Am.  O.S. , 36,  1269,  1914. 

8.  Meisenheimer.  Ber.,  4l,  3973,  19°8.  Ann., 335,  117,1911. 

9.  Wm.L. Jones.  Science,  46  (69)  493,  1917. 

10.  Michael.  J.  Am.  C.  S. , 42,1232,  1920. 

11.  Bray  and  branch.  J.  Am.  G.  S. , 35,  1441,  1913. 

12.  Hantzsch  and  Hilland.  Ber.,  31,  2°53,  1898. 

13*LQ&bry  de  Bruyn.  Receuil  Trav. , 13,  46,  1894. 

14.  Dunstan  and  Goulding.  Proc.,  10,  133,  1894. Chem. News. 69,308 
15-  Dunstan  and  Goulding.  J.C.S. , 69,  839,  1896. 

16. Lobry  de  Bruyn.  Rec.Trav.,  15,  135,  1896. 

17.  Dunstan  and  Goulding.  J.C.S.,  75,  793,  1399 

18.  Dunstan  and  Goulding.  J.C.S.,  75,  1004,  1899. 

19.  Jacob  Meisenheimer.  Ann.  397,  285,  1913. 


30. 


ACKNOWLEDGMENTS. 


In  concluding  this  thesis,  the  author  wishes  to 
express  his  appreciation  of  the  assistance  given  by 
Dr.  W.  A.  Noyes, under  whose  guidance  this  work  has  been 
carried  out.  By  criticisms,  suggestions,  and  interest 
taken  in  the  problem,  Dr.  Noyes  has  contributed  much  toward 
the  successful  preparation  of  the  compounds. 

In  addition  the  author  is  indebted  to  Dr.  Roger  Adams, 
Dr.  J.  H.  Reedy,  and  Dr.  W.  H.  Rodebush  for  many  kind 
suggestions  and  criticisms. 


